Macrophage activation and immunomodulation by myeloperoxidase.

Myeloperoxidase (MyPo) is an enzyme found in neutrophils and monocytes that plays an important role in the microbicidal and cytocidal activities of these cells. The present studies show that this enzyme can also affect both capacities and functions of macrophages. When resident peritoneal macrophages from C57BL/6 mice were exposed to preparations of either human or canine enzyme in vitro, tumor necrosis factor (TNF) was released. The amount of TNF produced was dose dependent and could be neutralized with polyclonal anti-TNF. Low levels of interferon were also produced by these cells. In addition, exposure of murine macrophages in vitro to this enzyme resulted in increased ability to destroy 3T12 target cells. Intravenous injection of mice with myeloperoxidase induced the production of both TNF and interferon, which could be detected in the sera. Possible mechanisms of TNF induction include radical production by myeloperoxidase or ligand-receptor interaction by the binding of this enzyme to the mannosyl-fucosyl receptor. These results, when taken in their entirety, suggest that this enzyme can modulate the immune response through effects on macrophage function.